Chemical Properties
White Cyrstalline Solid
Originator
Hoechst Marion Roussel (Germany)
Uses
A sulfonylurea hypoglycemic agent. Used as an antidiabetic
Uses
For concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
Definition
ChEBI: Glimepiride is a sulfonamide, a N-acylurea and a N-sulfonylurea. It has a role as a hypoglycemic agent and an insulin secretagogue.
Manufacturing Process
By heating of a mixture of 3-ethyl-4-methyl-2-pyrrolone and 2-
phenylethylisocyanate at 150°C is obtained 3-ethyl-4-methyl-2-oxo-3-
pyrroline-1-(N-2-phenylethyl)-carboxamide, melting point 106°-108°C. Then
the carboxamide are introduced in portions at 30°C into chlorosulfonic acid,
and agitated for 1 hour at 40°C. The sulfochloride (melting point 172-175°C),
introduced into concentrated ammonia, and heated for 30 min on a steam
bath. The mixture of sulfonamide obtained (melting point 180°-182°C), of
acetone and K2CO3 are refluxed with agitation for 6 hours. Subsequently the
cyclohexyl isocyanate are added dropwise, and agitation is continued for 6
hours at boiling temperature. After standing overnight, the product is filtered,
the crystals obtained are treated with dilute hydrochloric acid, and again
filtered. It is prepared N-(4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-
carboxamido)ethyl]benzenesulfonyl)-N'-cyclohexyl urea; melting point 185°-
187°C (from acetone) (Glimepiride).
Brand name
Amaryl (Sanofi Aventis).
Therapeutic Function
Oral hypoglycemic
General Description
Glimepiride is 3-ethyl-2,5-dihydro-4-methyl-N-[2-[4-[[[[(trans-4-methylcyclohexyl)amino]-carbonyl]amino]sulfonyl]phenyl]ethyl]-2-oxo-1H-pyrrole-1-carboxamide; thiscompound can also be named as the urea—see precedingdiscussion (Amaryl, generic). Combinations are availablewith rosiglitazone in the United States (Avandaryl tablets;mg glimepiride/mg rosiglitazone as maleate salt: 1/4,2/4, 4/4, 2/8, 4/8); and with pioglitazone (Duetact tablets;mg glimepiride/ mg pioglitazone as hydrochloride salt:2/30, 4/30).
General Description
Glimepiride, 1-[[p-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)ethyl]phenyl]sulfonyl]-3-(trans-4-methylcyclohexyl)urea (Amaryl), is very similarto glipizide with the exception of their heterocyclic rings.Instead of the pyrazine ring found in glipizide, glimepiridecontains a pyrrolidine system. It is metabolized primarilythrough oxidation of the alkyl side chain of the pyrrolidine,with a minor metabolic route involving acetylation of theamine.
Biological Activity
Potent K ATP channel blocker and anti-diabetic agent. Inhibits pinacidil-activated cardiac K ATP channels with an IC 50 of 6.8 nM.
Biochem/physiol Actions
Glimepiride is a potent blocker of cardiac KATP channels activated by pinacidil with an IC50 of 6.8 nM.
Clinical Use
Non-insulin dependent diabetes mellitus
Veterinary Drugs and Treatments
Glimepiride may potentially be a useful adjunct in the treatment of
non-insulin dependent diabetes mellitus (NIDDM) in cats. Its duration
of action in humans allows it to be dosed once daily, which
could be of benefit in cats. It may also have fewer side effects than
glipizide in cats.
Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: effects enhanced by NSAIDs.
Antibacterials: effects enhanced by chloramphenicol,
sulphonamides, tetracyclines and trimethoprim;
effect reduced by rifamycins.
Anticoagulants: effect possibly enhanced by
coumarins; also possibly changes to INR.
Antifungals: concentration increased by fluconazole
and miconazole and possibly voriconazole.
Lipid-regulating drugs: possibly additive
hypoglycaemic effect with fibrates.
Sulfinpyrazone: enhanced effect of sulphonylureas.
Metabolism
The drug is extensively metabolised in the liver to two
main metabolites. The cytochrome P450 isoenzyme
CYP2C9 is involved in the formation of a hydroxy
derivative, which is further metabolised to a carboxy
derivative by cytosolic enzymes.
About 60% of a dose is eliminated in the urine and 40%
in the faeces.
